Frontiers in Chemical Biology Seminar
This event will take place on Zoom.
In vitro directed evolution allows biomolecules with new and useful properties to be
engineered—mimicking natural evolution on an experimentally accessible time scale by
creating large libraries of DNA mutants using PCR and then carrying out a high-throughput
assay for variants with improved function. To provide a breakthrough in the complexity of
libraries that can be readily searched experimentally for synthetic biology and to allow
systems to be directly engineered in the cell, my laboratory is engineering S. cerevisiae so
that both the mutagenesis and selection steps of directed evolution can be carried out entirely
in vivo, under conditions of sexual reproduction. We have built a modular chemical
complementation assay, which provides a selection for diverse chemistry beyond that natural
to the cell using themes and variations on the yeast two-hybrid assay. In addition, we devised
a heritable recombination system, for simultaneous mutagenesis and selection in vivo under
conditions of sexual reproduction. Finally, we have begun to utilize these mutagenesis and
selection technologies to engineer yeast to carry out new functions themselves ranging from
being a biosensor, to a therapeutic, to a self-organizing community.